Summary: In adults with type 2 diabetes, a small double-blind randomized trial (n=66, Iran) compared empagliflozin, sitagliptin, and metformin over 12 weeks. Empagliflozin produced the largest numerical falls in HbA1c (-1.8% vs -1.35% with sitagliptin and -0.69% with metformin) and fasting glucose (-23.1 mg/dl), but the statistically significant advantages were demonstrated against the metformin arm, not against sitagliptin.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with type 2 diabetes mellitus; randomized double-blind trial, single centre, Iran (IRCT20191231045959N1). Reported per-arm n approximately 22 (total around 66). |
| Intervention | Empagliflozin arm over 12 weeks (approx. n=22). |
| Comparison | Two comparator arms: sitagliptin and metformin (each approx. n=22). The reported significance tests are empagliflozin versus metformin. |
| Outcome | Within-arm HbA1c fall: empagliflozin -1.8%, sitagliptin -1.35%, metformin -0.69%. Fasting glucose fall: -23.1, -16.15, -15.25 mg/dl respectively. Empagliflozin vs metformin: HbA1c P=0.037; FBS P=0.027; weight -4.1 vs -0.90 kg, P=0.044. Empagliflozin vs metformin adjusted mean differences: triglycerides -12.91 mg/dl (95% CI 6 to 31.82; P=0.001), HDL-c +6.47 mg/dl (95% CI 2.93 to 10.01; P=0.010), SBP -8.27 mmHg (95% CI -13.31 to -3.23; P=0.001), DBP -13.37 mmHg (95% CI -16.42 to -10.32; P=0.001). No statistically significant empagliflozin-versus-sitagliptin difference is reported in the abstract, and no genitourinary infection or other safety outcome is reported. No ARR/NNT applicable (continuous outcomes). |
Empagliflozin vs Sitagliptin vs Metformin
RCT · type 2 diabetes · 12 weeks
Versus metformin, empagliflozin add-on cut HbA1c, weight, and blood pressure and raised HDL over 12 weeks. No significant edge over sitagliptin was shown, and the trial is too small and short for outcome claims.
Expert Commentary
This small, single-centre, three-arm randomized trial confirms what mechanism already predicts: over 12 weeks, empagliflozin lowered fasting glucose, weight, blood pressure, and triglycerides and raised HDL more than metformin alone, with modest glycaemic gains over baseline. The verdict, however, is that the headline cannot be read as empagliflozin beating sitagliptin. The abstract reports significant differences only for the empagliflozin-versus-metformin contrast; the empagliflozin-versus-sitagliptin comparison, which the title implies, is not shown to be statistically significant, and the numerical HbA1c gap between the two active agents is small (-1.8% vs -1.35%). The dominant limitation is sample size: with roughly 22 patients per arm and only 12 weeks of follow-up, the study is underpowered to separate two effective drugs and far too short to speak to the cardiovascular or renal outcomes for which empagliflozin is actually valued. Can I use this with my patients? Cautiously, and only to reinforce existing practice: for a patient with type 2 diabetes who also carries excess weight, hypertension, or an unfavourable lipid profile, empagliflozin remains a rational add-on, but this trial adds little beyond confirming direction. It does not establish superiority over a DPP-4 inhibitor on hard outcomes. No safety signal, including the genitourinary infection risk inherent to this drug class, is reported here, so prescribers must rely on prior evidence. Larger, longer, adequately powered head-to-head trials with prespecified active-comparator contrasts are needed before any ranking claim is made.
References
Mesri Alamdari N, Barghaman M, Roshanravan N, Mobasseri M, Tutunchi H, Baharami A, et al. Comparison of the effects of empagliflozin and sitagliptin, as an add-on to metformin, on cardio-metabolic and glycemic parameters of patients with type 2 diabetes mellitus: a randomized, double-blind clinical trial. BMC Res Notes. 2025;18(1):339. doi:10.1186/s13104-025-07214-2